The Journal of Neuroscience, December 1, 2001, 21(23):9092-9100
Opioid Receptor Modulation of a Metabolically Sensitive Ion
Channel in Rat Amygdala Neurons
Xueguang
Chen,
Hector G.
Marrero, and
Jonathan E.
Freedman
Department of Pharmaceutical Sciences, Northeastern University,
Boston, Massachusetts 02115
We have used single-channel patch-clamp recordings to study opiate
receptor effects on freshly dissociated neurons from the rat
amygdalohippocampal area (also called the posterior nucleus of the
amygdala), an output nucleus of the amygdala implicated in appetitive
behaviors. Dissociated cells included a distinct subpopulation that was
30-40 µm in diameter, multipolar or pyramidal in shape, and
immunoreactive for neuron-specific enolase, µ opioid receptors, and
galanin. In whole-cell perforated-patch recordings, these cells
responded to low concentrations of µ opioid agonists with a
hyperpolarization. In cell-attached single channel recordings, these
cells expressed a large variety of K+-permeable ion
channels, including 20-100 pS inward rectifiers and 150-200 pS
apparent Ca2+-activated K+
channels, none of which appeared sensitive to the presence of opioid
drugs. In contrast, a 130 pS inwardly rectifying channel was
selectively activated by µ opioid receptors in this same
subpopulation of cells and was active only in the presence of opioid
agonists, and inhibited in the presence of antagonists. Channels
identical to the 130 pS channel in conductance and voltage sensitivity
were activated in the absence of opioids, when the cells were treated with glucose-free medium or with the metabolic inhibitor rotenone. The
sulfonylurea drug tolbutamide inhibited 130 pS channel openings elicited by opioids. Thus, a subpopulation of amygdala projection neurons expresses a metabolically sensitive ion channel that is selectively modulated by opiate receptors. This mechanism may allow
opioid neurotransmitters to regulate ingestive behaviors, and thus,
opiate drugs to influence reward pathways.
Key words:
amygdala; patch-clamp; potassium channel; opiate
receptor; opioid receptor; galanin; sulfonylurea; addiction; satiety
Copyright © 2001 Society for Neuroscience 0270-6474/01/21239092-09$05.00/0